Biomedical subjects

Ariel L Barkan

Publications and source records attributed to Ariel L Barkan.

24 records · Page 2Linked to original sources

PubMed2003

Ghrelin secretion in humans is sexually dimorphic, suppressed by somatostatin, and not affected by the ambient growth hormone levels.

We studied plasma ghrelin and GH concentrations over a 24-h period in young healthy men and women and in patients with acromegaly. Healthy subjects were restudied after administration of GH-lowering agents, octreotide or GHRH antagonist. Ghrelin concentrations in women studied during the late follicular stage of the cycle were about 3-fold higher than in men. Suppression of GH secretion by GHRH antagonist did not alter ghrelin concentration profiles. In the presence of high GH levels (acromegaly), ghrelin levels were similar to those found in healthy men. Administration of somatostatin analog octreotide suppressed both GH and ghrelin concentration profiles. We conclude that: 1) ghrelin secretion is sexually dimorphic in humans, with women in the late follicular stage having higher levels than men; 2) ghrelin secretion is suppressed by somatostatin; and 3) GH has no influence over ghrelin secretion.

Acromegaly↗

PubMed2003

Sexual dimorphism of growth hormone (GH) regulation in humans: endogenous GH-releasing hormone maintains basal GH in women but not in men.

GH secretory patterns in humans are sexually dimorphic in terms of pulse regularity, amplitude of the diurnal rhythm, and magnitude of basal (trough) secretion. The neuroendocrine mechanisms of gender-specific GH regulation in humans are currently unknown, but the interpulse GH levels are generally assumed to be controlled by somatostatin. In rats, however, administration of antiserum to GHRH lowers GH interpulse levels in females but not males. In this study, using a competitive antagonist to GHRH in humans, we investigated whether endogenous GHRH has differential, gender-specific effects on the interpulse GH levels. Six healthy men and five healthy women (20-28 yr old) who were nonobese, did not smoke, and were on no medications known to influence GH secretion were studied. Each served as his or her own control during an infusion of GHRH antagonist or saline for a 27-h period. A control bolus of GHRH was given near the end of the infusion. In both sexes during GHRH antagonist infusion, mean GH, pulse amplitude, and GH response to GHRH decreased significantly, whereas pulse frequency remained unchanged. However, during the GHRH antagonist infusion, trough GH did not significantly change in men (P = 0.54) but significantly decreased in women (P = 0.008). Deconvolution analysis confirmed the lack of a significant change in basal secretion in men (P = 0.81) as opposed to women (P = 0.006). We conclude that sexual dimorphism in the neuroendocrine regulation of GH secretion in humans involves a differential role of endogenous GHRH in maintaining baseline GH.

Adult↗

PubMed2003

Somatostatin analogs in medical treatment of acromegaly.

Although acromegaly remains a disease primarily addressed by pituitary microsurgery, most patients require secondary treatment for persistent growth hormone (GH) hypersecretion and elevated serum insulin-like growth factor-1 (IGF-1) concentrations following adenomectomy. Persistently abnormal serum GH and IGF-1 can be reduced to normal concentrations in better than half of post-surgery acromegalics using the pharmacologic treatments available at present, the dopamine agonists (DA) and somatostatin (SST) analogs. The long-acting SST analogs octreotide LAR and lanreotide SR have become the mainstay of medical treatment for acromegaly, having largely supplanted DA agents since the introduction of bromocriptine for the suppression of GH secretion in the 1970s. The DA cabergoline may be effective in up to half of patients, however, in particular those patients whose tumors cosecrete prolactin. On the horizon is the GH-receptor antagonist pegvisomant, which is expected to enable the reduction of serum IGF-1 to the normal range in the vast majority of postoperative acromegaly patients, representing a revolutionary development in the medical treatment of this disease. We here review the choices available to the endocrinologist in the pharmacologic treatment of acromegaly, focusing upon the SST analogs.

Acromegaly↗

PubMed2002

Medical management of growth hormone-secreting pituitary adenomas.

The primary treatment of acromegaly remains transsphenoidal adenomectomy, yet the tissue overgrowth of acromegaly often progresses following surgery, and responds to radiotherapy only after significant delay. Persistently elevated serum growth hormone (GH) and insulin-like growth factor-I (IGF-I) concentrations can be normalized in about half of post-surgery acromegalics using the pharmacologic alternatives presently available, the dopamine agonists (DA) and somatostatin (SST) analogs. Cabergoline, the most efficacious DA, normalizes IGF-I in approximately 37% of patients, whereas the long-acting SST analogs, Octreotide LAR and Lanreotide SR, do so in 66%. Significant tumor shrinkage may be attained with SST analogs in particular, and when necessary, the primary medical treatment of acromegaly may be successfully addressed with this class of drugs. Greatly enhanced efficacy is expected from the GH receptor antagonist pegvisomant, which is nearing market availability and will enable the normalization of serum IGF-I in virtually all patients treated. We review here the pharmacologic treatments of excessive GH secretion.

Adenoma↗

PubMed2002

Current status and future opportunities for controlling acromegaly.

Growth-hormone (GH) secreting adenomas, including acromegaly, account for approximately one-sixth of all pituitary adenomas and are associated with mortality rates at least twice that of the general population. The ultimate goal of therapy for acromegaly is normalization of morbidity and mortality rates achieved through removal or reduction of the tumor mass and normalization of insulin-like growth factor I (IGF-I) levels. Previously published efficacy results of current treatment modalities (surgery, conventional radiation, and medical therapy with dopamine agonists and somatostatin analogs) are often difficult to compare because of the different criteria used to define cure (some of which are now considered inadequate). For each of these modalities, pooled data from a series of acromegaly studies were reviewed for rates of IGF-I normalization, a currently accepted definition of cure. The results showed overall cure rates of approximately 10% for bromocriptine, 34% for cabergoline, 36% for conventional radiation, 50-90% for surgery for microadenomas and less than 50% for macroadenomas, and 54-66% for octreotide. These cure rates based on IGF-I normalization are generally less than those reported for cure based solely on GH levels. Novel new therapies for acromegaly include the somatostatin analog, lanreotide, Gamma Knife radiosurgery, and pegvisomant, the first in its class of new GH receptor antagonists. Although it does not appear that Gamma Knife radiosurgery results in significantly higher cure rates or fewer complications, it does provide a notable improvement in delivery compared with conventional radiation. Early studies have reported IGF-I normalization in 48% of lanreotide-treated patients and up to 97% of pegvisomant-treated.

Acromegaly↗

PubMed2002

Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up.

The biochemical diagnosis of acromegaly is conventionally based on elevated plasma GH levels that fail to suppress after an oral glucose load. We studied 16 newly diagnosed patients with acromegaly with normal mean plasma GH but elevated age and gender-adjusted plasma IGF-I concentrations (476 +/- 29 microg/liter, mean +/- SE). Plasma GH was sampled every 10 min for 24 h, and an oral glucose tolerance test was performed. The control group included 46 healthy subjects. All patients had 24-h mean GH values that overlapped with those of the healthy controls. Mean plasma GH was less than 2.5 microg/liter in 12 patients. Patients had higher 24-h nadir GH values than healthy controls (P < 0.001). During the oral glucose tolerance test, nadir plasma GH was less than 1 micro g/liter in eight patients. Plasma IGF-I normalized in 11 of 14 patients after transsphenoidal surgery. Four patients with normal IGF-I after transsphenoidal surgery were restudied. Mean and nadir GH decreased in all of them. In our experience in many patients with acromegaly, the diagnosis could be missed if only the existing GH-based criteria are used. Revised GH criteria in combination with plasma IGF-I should be used for the diagnosis and follow-up of acromegaly.

Acromegaly↗